Evaluation of the sub-acute toxicity of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk mushroom

Ethnopharmacological relevance

Lignosus rhinocerus (known locally as ‘Tiger Milk mushroom’) is the most important medicinal mushroom used by the indigenous communities of Malaysia to treat fever, cough, asthma, cancer, food poisoning and as a general tonic. The sclerotium of the mushroom is the part with medicinal value. Lignosus rhinocerus was hitherto unexploited commercially because of limited supply. Recently, the mushroom was successfully cultivated.

Materials and methods

Sprague Dawley rats (5 rats/group/sex) were fed orally with 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. Sclerotial powder was orally administered once daily and consecutively for 28 days. Body weight of each animal was measured and any gross behavioral change was observed daily. Hematological and clinical biochemical parameters as well as histopathological analysis were carried out on 29th day.

Results

The results showed that oral administration of the sclerotial powder at daily dose of up to 1000 mg/kg had no adverse effect on the growth rate, hematological and clinical biochemical parameters (including renal and liver function parameters). Histological studies showed that the treatments did not induce any pathological changes in the liver, kidney, heart, spleen and lung of the animals.

Conclusion

In conclusion, our results show that there was no treatment-related sub-acute toxicity in rats following 28-days oral administration of 250, 500 and 1000 mg/kg TM02, 1000 mg/kg TM03 as well as 1000 mg/kg wild type Lignosus rhinocerus sclerotial powder. As the highest tested dose of 1000 mg/kg was not associated with any toxicity concern, the NOAEL dose is higher than 1000 mg/kg.     

Mechanisms of the dilator action of the Erigerontis Herba on rat aorta

Ethnopharmacological relevance

Erigerontis Herba is widely used as a traditional Chinese medicine and is commonly used for neuroprotection and vascular protection.

Aim of study

In this study, the vasodilator effects of Erigerontis Herba (DZXX) were investigated using rat isolated aorta rings.

Material and method

The involvement of endothelium in the vasorelaxation was studied by comparing response of endothelium-intact and endothelium-denuded aorta rings which precontracted with U46619. The involvement of K⁺ channels was studied by pretreatment of the aorta rings with various K⁺ channel inhibitors. The involvement of Ca²⁺ channel was studied by incubating aorta rings with Ca²⁺-free solution, primed with U46619 prior to elicit contraction by addition of Ca²⁺ solution.

Results

DZXX (0.2–2 mg/ml) induced a concentration-dependent relaxation on U44619-precontracted aorta rings with EC₅₀ of 0.354±0.036 mg/ml. Removal of endothelium or pretreatment with a BK_Ca inhibitor iberiotoxin, K_IR inhibitor barium chloride or K_v inhibitor 4-aminopyridine produced no effect on the DZXX-induced vasorelaxation. However, pretreatment with a K_ATP inhibitor glibenclamide or a non-selective K⁺ channel inhibitor tetraethylammonium produced significant inhibition on the DZXX-induced vasorelaxation by 29.9% and 21.3%, respectively. Pretreatment with DZXX (0.4, 1.2 and 2 mg/ml) produced a concentration-dependent inhibition on Ca²⁺-induced vasoconstriction.

Conclusions

These results suggest that the vasodilator effect of DZXX was endothelium-independent, mediated by decreasing the influx of Ca²⁺ by calcium channel inhibition and increasing the influx of K⁺ by opening of a K_ATP channel.     

Association between tuberculosis infections and non-pulmonary malignancies: a nationwide population-based study

Background:

In addition to lung cancers, tuberculosis infections have been associated with increased risk of non-pulmonary malignancies in case reports. Our population-based study employed standardized incidence ratios (SIRs) to systemically survey non-pulmonary cancer risks after tuberculosis infections.

Methods:

Data of patients who had newly diagnosed tuberculosis, were aged 20 years or older, and had no prior cancer or tuberculosis were sampled from the Taiwan National Health Insurance database between 2000 and 2010. SIRs compared cancer incidence in patients with tuberculosis infections to the general population. SIRs of specific cancers were further analyzed with respect to gender and time after tuberculosis infections.

Results:

After a follow-up period of 28 866 person–years, 530 tuberculosis cases developed cancers compared with 256 cases in the general populations (2.07, 95% confidence interval (CI), 1.90–2.26). The SIR of non-pulmonary malignancies was also increased (1.71, 95% CI, 1.54–1.90). For males, SIRs were increased within 1 year after tuberculosis diagnosis for the following cancers: head and neck, esophageal, colorectal, liver, lung, melanomas, and Hodgkin''s disease. SIRs were increased for liver, biliary, lung, and bladder cancers beyond the first year after tuberculosis diagnosis. For females, SIRs were increased for leukemia, esophageal, and lung cancers within the first year, and only for leukemia beyond 1 year post diagnosis.

Conclusion:

Having found increased risks of several cancers that differ with gender and time after tuberculosis diagnosis, physicians may consider these factors in patients following tuberculosis diagnosis.     

Cyclopeptide RA-V inhibits angiogenesis by down-regulating ERK1/2 phosphorylation in HUVEC and HMEC-1 endothelial cells

BACKGROUND AND PURPOSE

Anti-angiogenic agents have recently become one of the major adjuvants for cancer therapy. A cyclopeptide, RA-V, has been shown to have anti-tumour activities. Its in vitro anti-angiogenic activities were evaluated in the present study, and the underlying mechanisms were also assessed.

EXPERIMENTAL APPROACH

Two endothelial cell lines, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1), were used. The effects of RA-V on the proliferation, cell cycle phase distribution, migration, tube formation and adhesion were assessed. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant molecules.

KEY RESULTS

RA-V inhibited HUVEC and HMEC-1 proliferation dose-dependently with IC₅₀ values of 1.42 and 4.0 nM respectively. RA-V inhibited migration and tube formation of endothelial cells as well as adhesion to extracellular matrix proteins. RA-V treatment down-regulated the protein and mRNA expression of matrix metalloproteinase-2. Regarding intracellular signal transduction, RA-V interfered with the activation of ERK1/2 in both cell lines. Furthermore, RA-V significantly decreased the phosphorylation of JNK in HUVEC whereas, in HMEC-1, p38 MAPK was decreased.

CONCLUSIONS AND IMPLICATIONS

RA-V exhibited anti-angiogenic activities in HUVEC and HMEC-1 cell lines with changes in function of these endothelial cells. The underlying mechanisms of action involved the ERK1/2 signalling pathway. However, RA-V may regulate different signalling pathways in different endothelial cells. These findings suggest that RA-V has the potential to be further developed as an anti-angiogenic agent.     

Age-Stratified Model to Assess Health Outcomes of COVID-19 Vaccination Strategies,Ghana

We assessed the effect of various COVID-19 vaccination strategies on health outcomes in Ghana by using an age-stratified compartmental model. We stratified the population into 3 age groups: <25 years, 25–64 years, and ≥65 years. We explored 5 vaccination optimization scenarios using 2 contact matrices, assuming that 1 million persons could be vaccinated in either 3 or 6 months. We assessed these vaccine optimization strategies for the initial strain, followed by a sensitivity analysis for the Delta variant. We found that vaccinating persons <25 years of age was associated with the lowest cumulative infections for the main matrix, for both the initial strain and the Delta variant. Prioritizing the elderly (≥65 years of age) was associated with the lowest cumulative deaths for both strains in all scenarios. The consensus between the findings of both contact matrices depended on the vaccine rollout period and the objective of the vaccination program.     

Semisupervised white matter hyperintensities segmentation on MRI

This study proposed a semisupervised loss function named level‐set loss (LSLoss) for cerebral white matter hyperintensities (WMHs) segmentation on fluid‐attenuated inversion recovery images. The training procedure did not require manually labeled WMH masks. Our image preprocessing steps included biased field correction, skull stripping, and white matter segmentation. With the proposed LSLoss, we trained a V‐Net using the MRI images from both local and public databases. Local databases were the small vessel disease cohort (HKU‐SVD, n = 360) and the multiple sclerosis cohort (HKU‐MS, n = 20) from our institutional imaging center. Public databases were the Medical Image Computing Computer‐assisted Intervention (MICCAI) WMH challenge database (MICCAI‐WMH, n = 60) and the normal control cohort of the Alzheimer''s Disease Neuroimaging Initiative database (ADNI‐CN, n = 15). We achieved an overall dice similarity coefficient (DSC) of 0.81 on the HKU‐SVD testing set (n = 20), DSC = 0.77 on the HKU‐MS testing set (n = 5), and DSC = 0.78 on MICCAI‐WMH testing set (n = 30). The segmentation results obtained by our semisupervised V‐Net were comparable with the supervised methods and outperformed the unsupervised methods in the literature.     

Correction: Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease

Correction for ‘Discovery of 8-prenylnaringenin from hop (Humulus lupulus L.) as a potent monoacylglycerol lipase inhibitor for treatments of neuroinflammation and Alzheimer’s disease’ by Min-Che Tung et al., RSC Adv., 2021, 11, 31062–31072, https://doi.org/10.1039/D1RA05311F.

The authors regret that the name of one of the authors (Hsing-Mien Hsu) was shown incorrectly in the original article. The corrected author list is as shown above.The authors also regret an incorrect version of Fig. 7 was included in the original article. The correct version of Fig. 7 is presented below.Open in a separate windowFig. 7The dose-dependent inhibitions of the identified inhibitors against hMAGL.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Evaluation of retinal nerve fiber layer,ganglion cell layer,and optic nerve head morphological parameters in patients with obstructive sleep apnea and comparison with normal population

Purpose:To compare the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and optic nerve head (ONH) morphological parameters between obstructive sleep apnea (OSA) patients and age-matched controls using spectral domain optical coherence tomography (SD-OCT).Methods:This case control study was conducted in a multi-specialty tertiary care hospital from 2014 to 2016. Patients diagnosed to have OSA by overnight polysomnography were included in the study. Fifty eyes of 25 OSA patients with clinically normal optic disc were compared with 50 eyes of age-matched controls. The study population underwent detailed ophthalmological evaluation including SD-OCT.Results:There was significant thinning of the superior, inferior, and average RNFL in the OSA group when compared to controls. GCL analysis also showed a significant thinning of the six sectors as well as average and minimum ganglion cell layer + inner plexiform layer in OSA patients. The optic nerve head rim area was significantly decreased in OSA patients when compared to controls.Conclusion:OSA patients even with clinically normal optic disc showed significant decrease in the RNFL thickness, GCL thickness, and rim area when compared to age-matched controls. Hence, these patients constitute a high-risk population who need to be regularly screened and followed up for ocular co-morbidities.